Immune Dys-regulation in HIV-infected women with heavy alcohol consumption

描述（由申请人提供）：饮酒在艾滋病毒感染者中很常见，大量饮酒与艾滋病毒疾病进展加快和健康状况不佳有关。本研究将探讨重度饮酒的HIV感染妇女CD4 T细胞下降和HIV疾病进展的机制。酒精可能引起免疫功能障碍的一种机制是通过诱导微生物易位。我们将研究超过10年观察期的慢性累积暴露（数量x持续时间）是否与更快速的CD4 T细胞下降和免疫功能障碍（即免疫激活水平恶化、炎症和免疫衰老）相关，从而导致艾滋病和非艾滋病合病的早期出现。我们将检验我们的假设，即使用NIAAA有害饮酒标准定义的大量饮酒（对于女性，每周70杯或每次100杯）会破坏肠道屏障，导致微生物易位，从而增强全身免疫激活，炎症和衰老；所有导致CD4 t细胞下降和HIV疾病进展的事件。我们将在纵向队列（妇女跨机构艾滋病毒研究）的生物标本中回顾性地进行这项研究。作为与该联合体中其他o -1相连的次要目标；在一项关于酒精减少药物纳曲酮的随机临床试验中，我们将检查在HIV感染的重度饮酒者中，纳曲酮是否可以改善酒精相关的免疫失调。我们将在从事危险饮酒的艾滋病毒感染妇女中建立免疫标记（易位、免疫激活、炎症和免疫衰老）的储存库和数据库；这可以用于未来与酒精和艾滋病毒相互作用相关的转化研究：观察性或机制性。该项目汇集了来自HIV/AIDS领域领先临床医生、行为科学家、流行病学家和免疫学家的跨学科专业知识，以成功实现本研究的目的和目标。

DESCRIPTION (provided by applicant): Alcohol consumption is common in HIV infected individuals and heavy alcohol consumption has been associated with accelerated HIV disease progression and poor health outcomes. This proposal will investigate mechanism underlying CD4 T cell decline and HIV disease progression in HIV infected women who engage in heavy alcohol consumption. One mechanism by which alcohol may cause immune dysfunction is by inducing microbial translocation. We will examine whether chronic cumulative exposure (amount x duration) over 10 years of observation period is associated with more rapid CD4 T cell decline and immune dysfunctionality namely exacerbation in levels of immune activation, inflammation and immune senescence leading to early advent of AIDS and Non AIDS co-morbidities. We will test our hypothesis that heavy alcohol consumption, defined using NIAAA criteria for hazardous drinking (for women, >7drinks/week or >3 drinks per occasion), disrupts the gut barrier causing microbial translocation which enhances systemic immune activation, inflammation and senescence; all events that contribute to CD4 T-cell decline and HIV disease progression. We will conduct this study retrospectively in bioreposited specimens from the longitudinal cohort, the Women's Interagency HIV Study. As a secondary aim linked to the other UO-1 in this consortium; a randomized clinical trial on alcohol reduction medication naltrexone, we will examine in subset of HIV infected heavy drinkers, whether alcohol reduction medication, naltrexone improves alcohol related immune dysregulation. We will create a repository and database of immune markers (translocation, immune activation, inflammation, and immune senescence) in HIV infected women who engage in hazardous drinking; which can be used for future translational studies related to alcohol and HIV interaction: observational or mechanistic. This project has a cross discipline expertise, from leading clinicians in the HIV/AIDS field, behavioral scientists, epidemiologist, and immunologist for successful implementation of the aims and objectives of this study.